In 1973, Bliss et al. elucidated that a tetanic electric stimulation on the perforating fiber having a nerve ending in hippocampal dentate gyrus results in the sustained potentiation of subsequent response to an electric stimulation of dentate gyrus that is a postsynaptic cell. This phenomenon is called an LTP (long-term potentiation) and is recognized as a cell model of learning and memory (T. V. P. Bliss and G. L. Collingridge, Nature Vol. 361, page 31, 1993), wherein it is considered that learning and memory is not stored in a specific RNA or peptide but is based on a long-term potentiation of synaptic transmission efficiency. LTP is considered to be the result of a long-term potentiation of neurotransmission, which is a plasticity forming process model of the central nervous system responsible for learning and memory. LTP is also considered to be involved in the onset of various nervous and mental diseases, such as epilepsy, ischemic encephalopathy, Alzheimer's disease and the like. Therefore, a substance that induces LTP expression has a potential of becoming a therapeutic or preventive drug for these nervous and mental diseases inclusive of dementia.
One of the various factors suspected of being involved in controlling LTP expression is arachidonic acid (J. H. Williams, J. Lipid. Mediat. Cell Signal., Vol. 14, page 331, 1996). Arachidonic acid is an unsaturated fatty acid produced by hydrolysis via prophospholipase A2 of phosphatidylcholine that is one of the membrane lipids, and the interaction with the activating pathway of protein kinase C has been drawing attention as to the involvement into the control of LTP expression (Y. Nishizuka, FASEB J, Vol. 9, page 484, 1995). It has been also suggested that arachidonic acid is involved in LTP-like potentiation of synaptic transmission by prolonging activation of neuronal nicotinic acetylcholine receptors (T. Nishizaki et. al., Molecular Brain Research, vol. 69, pp. 263-272, 1999).
Arachidonic acid is produced in the living body and quickly metabolized. Therefore, a stable effect over a long period of time cannot be expected.
To overcome this problem, a compound having an LTP-like potentiation of synaptic transmission, which allows slow metabolism in the body and which is capable of sustaining a stable LTP-like potentiation of synaptic transmission, has been desired.